Plasmids are extrachromosomal genetic elements found throughout the biological realm. In an experimental sense, they may be considered mini chromosomes and they represent excellent model systems for the study of many basic properties of chromosomes. DNA replication and its control are considered central processes in the study of cell biology and a full understanding of this subject is considered to be the likely arena of study leading to control of cancer (Kornberg, A.: Aspects of DNA replication. Cold Spring Harbor Symp. quant. Biol. 43:1-9 [1979]). Additionally, some plasmid gene products lead to enhanced pathogenicity, virulence or resistance to chemotherapeutic agents. Hence, plasmids are of intrinsic interest to a number of disciplines, including biochemistry, molecular biology, general and clinical microbiology and control of infectious diseases. Our research centers around plasmid F, a plasmid whose control of replication is very similar to control of bacterial chromosome replication. We have identified three incompatibility (inc) genes, genes that directly or indirectly also control F replication (copy number). In the present application, we seek further understanding of inc gene control of F DNA replication by production, characterization, and mapping of additional inc mutants; by determining a transcriptional map of F replication genes; by determining the roles and interactions of inc genes in regulating transcription of replication genes; and by biochemically characterizing and purifying inc gene products. Also, certain classes of inc mutants not only show increased copy numbers but also aberrant segregation at cell division. Through mutant analysis, we seek to prove or disprove the thesis that replication, its control, incompatibility and plasmid distribution are interlocking events. Finally, we will begin to develop and analyse an F replication system that has unique properties and potential advantages because of its association with the ColE1 replicon. Basically, these aims are designed to support the control of DNA replication.